The Shigella Type III Secretion Effector IpaH4.5 Targets NLRP3 to Activate Inflammasome Signaling.
The Shigella Type III Secretion Effector IpaH4.5 Targets NLRP3 to Activate Inflammasome Signaling.
复制标题
志贺氏菌 III 型分泌效应器 IpaH4.5 靶向 NLRP3 激活炎症小体信号转导
DOI：
10.3389/fcimb.2020.511798
复制
发表时间：
2020
影响因子：
5.7
通讯作者：
Wei C
中科院分区：
文献类型：
--
作者：
Wang X;Sun J;Wan L;Yang X;Lin H;Zhang Y;He X;Zhong H;Guan K;Min M;Sun Z;Yang X;Wang B;Dong M;Wei C
NLRP 3炎性体的激活需要NLRP 3的表达，NLRP 3的表达受到其直接识别微生物来源物质的能力的严格调节。尽管已经发现巨噬细胞中caspase-1通过NLRP 3和NLRC 4活化的参与，但志贺氏菌感染触发NLRP 3活化的准确机制仍然没有充分了解。在这里，我们证明了IpaH4.5，志贺氏菌T3 SS效应子，通过调节NLRP 3的表达，通过E3泛素连接酶活性的IpaH4.5触发炎性小体激活。首先，我们发现IpaH4.5与NLRP 3相互作用。结果，IpaH4.5调节NLRP 3蛋白的稳定性和炎性小体的活化。缺乏IpaH4.5的细菌诱导焦亡的能力显著降低。我们的研究结果确定了一个以前未被识别的目标IpaH4.5在炎症信号的调节和澄清的T3 SS效应细胞质反应的分子基础。
Activation of the NLRP3 inflammasome requires the expression of NLRP3, which is strictly regulated by its capacity to directly recognize microbial-derived substances. Even though the involvement of caspase-1 activation in macrophages via NLRP3 and NLRC4 has been discovered, the accurate mechanisms by which Shigella infection triggers NLRP3 activation remain inadequately understood. Here, we demonstrate that IpaH4.5, a Shigella T3SS effector, triggers inflammasome activation by regulating NLRP3 expression through the E3 ubiquitin ligase activity of IpaH4.5. First, we found that IpaH4.5 interacted with NLRP3. As a result, IpaH4.5 modulated NLRP3 protein stability and inflammasome activation. Bacteria lacking IpaH4.5 had dramatically reduced ability to induce pyroptosis. Our results identify a previously unrecognized target of IpaH4.5 in the regulation of inflammasome signaling and clarify the molecular basis for the cytosolic response to the T3SS effector.
登录
查看更多内容
Shigella Ipah家族效应子是研究致病细菌的多功能模型。
影响因子：
5.7
作者：
Ashida H;Sasakawa C
通讯作者：
Sasakawa C
影响因子：
3.3
作者：
Prajapati, Bhumika;Jena, Prasant Kumar;Seshadri, Sriram
通讯作者：
Seshadri, Sriram
影响因子：
9
作者：
Senerovic, L.;Tsunoda, S. P.;Goosmann, C.;Brinkmann, V.;Zychlinsky, A.;Meissner, F.;Kolbe, M.
通讯作者：
Kolbe, M.
影响因子：
14.2
作者：
Dadi, Harjit;Jones, Tyler A.;Roifman, Chaim M.
通讯作者：
Roifman, Chaim M.
影响因子：
4.4
作者：
Pelegrin, Pablo;Barroso-Gutierrez, Consuelo;Surprenant, Annmarie
通讯作者：
Surprenant, Annmarie